Plasma cell diseases: causes, symptoms, diagnosis, treatment

Plasma cell diseases (dysproteinemias; monoclonal gammopathies; paraproteinemias; plasma cell dyscrasias) are a group of diseases of unknown etiology, characterized by disproportionate proliferation of one clone of B cells, the presence of structurally and electrophoretically homogeneous (monoclinal) immunoglobulins or polypeptides in the blood serum or urine.

[ 1 ], [ 2 ]

Causes plasma cell diseases

The etiology of plasma cell diseases is unknown; they are characterized by disproportionate proliferation of a single clone. The result is a corresponding increase in the serum level of their product, monoclonal immunoglobulin (M-protein).

M-protein may contain both heavy and light chains, or only one type of chain. Antibodies exhibit some activity that may cause autoimmune damage to organs, especially the kidneys. When M-protein is produced, the production of other immunoglobulins usually decreases and immunity is thus impaired. M-protein can coat platelets, inactivate coagulation factors, increase blood viscosity, and also provoke bleeding by other mechanisms. M-protein can cause secondary amyloidosis. Clonal cells often infiltrate the bone matrix and bone marrow, leading to osteoporosis, hypercalcemia, anemia, and pancytopenia.

[ 3 ], [ 4 ]

Pathogenesis

After emerging in the bone marrow, undifferentiated B cells migrate to peripheral lymphoid tissues: lymph nodes, spleen, intestine, and Peyer's patches. Here they begin to differentiate into cells, each of which is capable of responding to a limited number of antigens. After encountering the appropriate antigen, some B cells undergo clonal proliferation into plasma cells. Each clonal plasma cell line is capable of synthesizing one specific antibody, an immunoglobulin consisting of one heavy chain (gamma, mu, alpha, epsilon, or delta) and one light chain (kappa or lambda). Slightly more light chains are normally produced, and urinary excretion of small amounts of free polyclonal light chains (< 40 mg/24 h) is normal.

[ 5 ], [ 6 ], [ 7 ]

Symptoms plasma cell diseases

Plasma cell diseases range from asymptomatic, stable conditions (in which only protein is detected) to progressive neoplasias (eg, multiple myeloma). Rarely, transient plasma cell diseases are associated with drug hypersensitivity (sulfonamides, phenytoin, penicillin), viral infections, and cardiac surgery.

Forms

Category	Symptoms	Disease	Comments and examples
Monoclonal gammopathy of undetermined significance	Asymptomatic Usually non-progressive	Associated with non-lymphoreticular tumors Associated with chronic inflammatory and infectious conditions Associated with various other diseases	Mainly carcinomas of the prostate, kidneys, gastrointestinal tract, mammary gland and bile ducts Chronic cholecystitis, osteomyelitis, tuberculosis, pyelonephritis, RA Lichen myxedema, liver disease, thyrotoxicosis, pernicious anemia, myasthenia gravis, Gaucher disease, familial hypercholesterolemia, Kaposi's sarcoma May occur in relatively healthy people; more common with age
Malignant plasma cell diseases	There are symptoms of the disease, progressive course	Macroglobulinia Multiple myeloma Non-hereditary primary systemic amyloidosis Heavy chain disease	IgM Most commonly IgG, IgA or light chains only (Bence Jones) Usually only light chains (Bence-Jones), but sometimes intact immunoglobulin molecules (IgG, IgA, IgM, IgD) IgG heavy chain disease (sometimes benign). IgA heavy chain disease. IgM heavy chain disease. IgD heavy chain disease
Transient plasma cell diseases			Associated with drug hypersensitivity, viral infections and cardiac surgery

[ 8 ], [ 9 ], [ 10 ]

Diagnostics plasma cell diseases

The presence of a plasma cell disorder is suspected when there is clinical manifestation (often anemia), elevated serum protein levels, or proteinuria, prompting further investigation with serum or urine protein electrophoresis that detects M-protein. M-protein is further analyzed by immunofixation electrophoresis to identify the heavy and light chain classes.

[ 11 ], [ 12 ], [ 13 ], [ 14 ], [ 15 ], [ 16 ]